5ja4

Crystal structure of human TONSL and MCM2 HBDs binding to a histone H3-H4 tetramerCrystal structure of human TONSL and MCM2 HBDs binding to a histone H3-H4 tetramer

Structural highlights

5ja4 is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Activity:	DNA helicase, with EC number 3.6.4.12
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[TONSL_HUMAN] Component of the MMS22L-TONSL complex, a complex that stimulates the recombination-dependent repair of stalled or collapsed replication forks. The MMS22L-TONSL complex is required to maintain genome integrity during DNA replication by promoting homologous recombination-mediated repair of replication fork-associated double-strand breaks. It may act by mediating the assembly of RAD51 filaments on ssDNA. Within the complex, may act as a scaffold.^[1] ^[2] ^[3] ^[4] [MCM2_HUMAN] Acts as component of the MCM2-7 complex (MCM complex) which is the putative replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity. Required for the entry in S phase and for cell division.^[5]

References

↑ O'Donnell L, Panier S, Wildenhain J, Tkach JM, Al-Hakim A, Landry MC, Escribano-Diaz C, Szilard RK, Young JT, Munro M, Canny MD, Kolas NK, Zhang W, Harding SM, Ylanko J, Mendez M, Mullin M, Sun T, Habermann B, Datti A, Bristow RG, Gingras AC, Tyers MD, Brown GW, Durocher D. The MMS22L-TONSL complex mediates recovery from replication stress and homologous recombination. Mol Cell. 2010 Nov 24;40(4):619-31. doi: 10.1016/j.molcel.2010.10.024. Epub 2010 , Nov 4. PMID:21055983 doi:http://dx.doi.org/10.1016/j.molcel.2010.10.024
↑ Duro E, Lundin C, Ask K, Sanchez-Pulido L, MacArtney TJ, Toth R, Ponting CP, Groth A, Helleday T, Rouse J. Identification of the MMS22L-TONSL complex that promotes homologous recombination. Mol Cell. 2010 Nov 24;40(4):632-44. doi: 10.1016/j.molcel.2010.10.023. Epub 2010 , Nov 4. PMID:21055984 doi:http://dx.doi.org/10.1016/j.molcel.2010.10.023
↑ O'Connell BC, Adamson B, Lydeard JR, Sowa ME, Ciccia A, Bredemeyer AL, Schlabach M, Gygi SP, Elledge SJ, Harper JW. A genome-wide camptothecin sensitivity screen identifies a mammalian MMS22L-NFKBIL2 complex required for genomic stability. Mol Cell. 2010 Nov 24;40(4):645-57. doi: 10.1016/j.molcel.2010.10.022. Epub 2010 , Nov 4. PMID:21055985 doi:http://dx.doi.org/10.1016/j.molcel.2010.10.022
↑ Ray P, Zhang DH, Elias JA, Ray A. Cloning of a differentially expressed I kappa B-related protein. J Biol Chem. 1995 May 5;270(18):10680-5. PMID:7738005
↑ Todorov IT, Pepperkok R, Philipova RN, Kearsey SE, Ansorge W, Werner D. A human nuclear protein with sequence homology to a family of early S phase proteins is required for entry into S phase and for cell division. J Cell Sci. 1994 Jan;107 ( Pt 1):253-65. PMID:8175912

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OCA

[1] O'Donnell L, Panier S, Wildenhain J, Tkach JM, Al-Hakim A, Landry MC, Escribano-Diaz C, Szilard RK, Young JT, Munro M, Canny MD, Kolas NK, Zhang W, Harding SM, Ylanko J, Mendez M, Mullin M, Sun T, Habermann B, Datti A, Bristow RG, Gingras AC, Tyers MD, Brown GW, Durocher D. The MMS22L-TONSL complex mediates recovery from replication stress and homologous recombination. Mol Cell. 2010 Nov 24;40(4):619-31. doi: 10.1016/j.molcel.2010.10.024. Epub 2010 , Nov 4. PMID:21055983 doi:http://dx.doi.org/10.1016/j.molcel.2010.10.024

[2] Duro E, Lundin C, Ask K, Sanchez-Pulido L, MacArtney TJ, Toth R, Ponting CP, Groth A, Helleday T, Rouse J. Identification of the MMS22L-TONSL complex that promotes homologous recombination. Mol Cell. 2010 Nov 24;40(4):632-44. doi: 10.1016/j.molcel.2010.10.023. Epub 2010 , Nov 4. PMID:21055984 doi:http://dx.doi.org/10.1016/j.molcel.2010.10.023

[3] O'Connell BC, Adamson B, Lydeard JR, Sowa ME, Ciccia A, Bredemeyer AL, Schlabach M, Gygi SP, Elledge SJ, Harper JW. A genome-wide camptothecin sensitivity screen identifies a mammalian MMS22L-NFKBIL2 complex required for genomic stability. Mol Cell. 2010 Nov 24;40(4):645-57. doi: 10.1016/j.molcel.2010.10.022. Epub 2010 , Nov 4. PMID:21055985 doi:http://dx.doi.org/10.1016/j.molcel.2010.10.022

[4] Ray P, Zhang DH, Elias JA, Ray A. Cloning of a differentially expressed I kappa B-related protein. J Biol Chem. 1995 May 5;270(18):10680-5. PMID:7738005

[5] Todorov IT, Pepperkok R, Philipova RN, Kearsey SE, Ansorge W, Werner D. A human nuclear protein with sequence homology to a family of early S phase proteins is required for entry into S phase and for cell division. J Cell Sci. 1994 Jan;107 ( Pt 1):253-65. PMID:8175912

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